This invention relates to generation of nitric oxide, and more particularly to the generation of nitric oxide for delivery to a patient.
Nitric oxide (xe2x80x9cNOxe2x80x9d) gas, also known as a nitrosyl radical, is a free radical that is an important signaling molecule in pulmonary vessels. Its importance was first recognized by Robert Furchgott who discovered that the Endothelium-derived Relaxing Factor (xe2x80x9cEDRFxe2x80x9d), a naturally occurring chemical produced by the endothelium cell lining of blood vessels from oxygen and the amino acid, L-arginine, was identical to NO. The NO diffuses into smooth muscle cells in the vascular wall and causes dilation of the blood vessel""s wall (xe2x80x9cvasodilationxe2x80x9d).
NO that diffuses into the blood vessel displaces oxygen from hemoglobin, to form methemoglobin. The bright red methemoglobin does not play a role in vasodilation.
Inhaling low levels of NO, such as in range of between 1 to 100 parts per million (xe2x80x9cppmxe2x80x9d), rapidly and safely decreases pulmonary artery hypertension in many patients without causing systemic hypotension. This result occurs without causing systemic hypotension because inhaled NO only dilates those pulmonary vessels that perfuse well-ventilated lungs. As a result, pulmonary gas exchange is improved while pulmonary vascular resistance is reduced and pulmonary blood flow is increased. In hypoxemic newborns with pulmonary hypertension, clinical studies have shown that delivering inhaled NO increases systemic oxygen levels and lessens the likelihood of extracorporeal membrane oxygenation.
Nitric oxide has also been observed to regulate cell proliferation. Recent studies suggest that inhaled NO selectively modulates the pulmonary artery""s cellular proliferative response that is associated with lung injury. These recent studies also indicate that inhaled NO can be applied to attenuate or prevent pulmonary artery disease in patients with injured lungs.
Nitric oxide plays an active and direct role during infection by protecting the host and destroying the microbe causing the infection. For example, an overproduction of NO during septic shock has been described as potentially being responsible for the systemic vasodilation that can occur during septic shock.
Nitric oxide also may be used as an anticoagulant if delivered to the blood. Trace amounts of NO administered to the blood function as a platelet inhibitor to reduce platelet activation. Therapeutic levels of NO may prove useful for chronic anti-platelet therapy for patients with implanted mechanical valves. Moreover, while NO has a fundamental role in the control of blood pressure and micro-vascular motility and aiding in killing foreign invaders in the immune response, as described above, it also is the final common mediator in penile erection, for example, as the basis of the drug Viagra. It also is believed to play a major factor in the mechanisms of long-term memory.
Indigenous NO, measured in exhaled breath, can be used as the basis for a diagnostic or monitoring test. For example, exhaled NO can be used as a non-invasive means of monitoring inflammation of the upper and lower respiratory tract. In the normal upper airways, the bulk of exhaled NO originates from the paranasal sinuses. Exhaled NO is increased by nasal allergies and asthmatic airways. Exhaled NO is decreased by cystic fibrosis, nasal polyposis, and chronic sinusitis.
Conventional NO therapy includes delivering a stream of high concentration NO gas and a stream of air, oxygen, or nitrogen, and combining the streams immediately before delivering the NO to the patient to provide NO to the patient at a therapeutic level of less than 100 ppm. The need to combine the streams immediately before delivery to the patient is a consequence of the reaction kinetics of NO with oxygen to preferentially produce nitrogen dioxide at ambient temperature, which then may be converted in the presence of water to nitric acid and nitrous acid, which are detrimental to a patient""s lungs.
Nitric oxide gas typically is stored in glass or metal containers or bottles at a high concentration, e.g., 800 ppm, in an oxygen-free environment. The inner surface of a container is polished or deactivated to prevent adsorption of NO on the walls of the container.
There are two reasons for the concentration in the container being eight to ten times higher than therapeutic levels. First, NO must be stored in an oxygen-free environment, such as a nitrogen environment. Accordingly, to provide 100 ppm of NO in air or oxygen, the NO and nitrogen stream of gas must be mixed and diluted with air or oxygen immediately before use. Second, gas bottles are expensive and cumbersome to transport, such that supplying the NO at a high concentration and having the user dilute the NO to a low concentration reduces the cost of otherwise supplying NO at a therapeutic level.
In one general aspect, a nitric oxide generation and delivery system for delivering nitric oxide to a patient to treat a medical condition includes a container, a nitric oxide generation chamber, and a pump. The container is configured to contain a nitrogen-containing compound. The nitric oxide generation chamber includes a heat source and is configured to generate nitric oxide from the nitrogen-containing compound. The pump is configured to transfer at least a part of the nitrogen-containing compound in the container to the nitric oxide generation chamber.
Implementations may include one or more of the following. For example, the medical condition may include vasoconstriction. The system may include a filter system that filters impurities from the nitric oxide, a cooling system that cools the nitric oxide, a monitoring system that monitors a concentration of nitric oxide and/or nitrogen dioxide, and a breathing tube connectable to the patient to deliver the nitric oxide to the patient.
The system also may include a control system that controls an operation of the pump to transfer the nitrogen-containing compound in the container to the nitric oxide generation chamber. The control system may control the operation of the pump to transfer the nitrogen-containing compound based on a signal received from a monitoring system that monitors a concentration of nitric oxide.
The nitrogen-containing compound may include ammonia. The nitrogen-containing compound and/or the ammonia may be in the form of solid, a gas, and/or a liquid.
The container may include a heater and/or a metering valve. The NO generation chamber may include a catalyst, such as nickel and/or a noble metal, and the catalyst may be heated.
The controller may control the operation of the pump to transfer the nitrogen-containing compound in the container to the nitric oxide generation chamber such that a therapeutic dose of nitric oxide is generated in the nitric oxide generation chamber. The therapeutic dose of the nitric oxide may be between approximately 1 ppm and 100 ppm nitric oxide, and more particularly, between approximately 20 ppm and 80 ppm nitric oxide. The container may include a container release mechanism that is configured to release the compound into a line such that the pump can pass a gas through the line to transfer the compound to the nitric oxide generation chamber. The container release mechanism may be one of a metered valve, a heater, or a variable diameter opening. The gas may be oxygen or air.
In another general aspect, treating a patient having a medical condition by using nitric oxide gas includes providing a stream of gas that includes a nitrogen-containing compound, reacting the nitrogen-containing compound in a nitric oxide generation chamber to produce a stream of gas that includes nitric oxide, and delivering the stream of gas that includes nitric oxide from the nitric oxide generation chamber to the patient. The nitric oxide generation and delivery system provides considerable advantages. For example, the system generates NO gas at the concentration at which the NO gas will be delivered to the patient, and immediately delivers the NO gas to the patient. Moreover, the system generates NO gas at a location near the patient. Thus, there is a drastic reduction in the quantity of nitrogen dioxide that will be produced between the time the NO is generated and the time at which the NO reaches the patient because that time is short.
The system also does not involve multiple gas canisters and mixing equipment, which are burdensome to move and potentially dangerous. Instead, the system is portable and, for example, can be used beside the bed, attached to a wheel chair, in an ambulatory harness, or under any conditions as dictated by each patient""s individual situation.
Other features and advantages will be apparent from the description, the drawings, and the claims.